Colak A, Soy O, Karaoglan A, Akdemir O, Kokturk S, Sagmanligil A, Tasyurekli M
Department of Neurosurgery, School of Medicine, Maltepe University, Istanbul, Turkey.
Cent Eur Neurosurg. 2009 Nov;70(4):187-94. doi: 10.1055/s-0029-1202357. Epub 2009 Oct 22.
The pathogenesis and treatment of cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) remains a matter of discussion. The authors investigated the efficacy of GYKI 52466, a 2,3-benzodiazepine that is a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptor antagonist, in a rat femoral artery vasospasm model.
Twenty-seven Wistar albino rats were used in this study. The animals were divided into 3 groups of 9 animals each: sham-operated control (group 1), vasospasm group (group 2), and vasospasm-plus-treatment group (group 3). In groups 2 and 3, autologous blood (0.1 mL) was applied to a 1-cm segment of the femoral artery, which was then wrapped with a silicone cuff. One minute after blood application, the rats in group 3 received an intraperitoneal injection of 15 mg/kg GYKI 52466 every 12 h for 24 h. Responses to blood application and treatment were evaluated with light and electron microscopy examinations of femoral artery specimens at 72 h.
On light microscope examination, the mean diameters of the arterial lumens in groups 1, 2, and 3 were 514.47+/-15.3, 317.63+/-12.1, and 503.91+/-9.6 microm, respectively. At 24 h, the mean arterial wall thickness in group 1 was 77.69+/-4.2 microm. This mean thickness in group 2 increased to 164.82+/-9.1 microm. After GYKI treatment in group 3, the mean arterial wall thickness measured 95.37+/-5.3 microm. In group 2 rats, electron microscopy demonstrated various changes including marked luminal narrowing and increased wall thickness in the femoral arterial wall. The most striking finding were the degenerative changes in the endothelium, which presented as a corrugated appearance of the internal elastic lamina. Rats in group 3 had endothelia that were slightly constricted and smooth muscle cells that were relaxed; changes in the vessel wall and internal elastic lamina were less prominent in these rats than in the rats of group 2.
The results of the present study suggest that GYKI 52466 inhibited AMPA receptors and induced relaxation of smooth muscle cells in the wall of the femoral artery in a rat model. This substance may be a protective and therapeutic agent in the treatment of cerebral vasospasm.
蛛网膜下腔出血（SAH）后脑血管痉挛（CV）的发病机制和治疗仍存在争议。作者在大鼠股动脉痉挛模型中研究了GYKI 52466（一种2,3-苯并二氮䓬，是一种选择性且强效的α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体拮抗剂）的疗效。
本研究使用了27只Wistar白化大鼠。动物被分为3组，每组9只：假手术对照组（第1组）、血管痉挛组（第2组）和血管痉挛加治疗组（第3组）。在第2组和第3组中，将自体血（0.1 mL）注入股动脉1 cm长的节段，然后用硅胶套包裹。注入血液1分钟后，第3组大鼠每12小时腹腔注射15 mg/kg GYKI 52466，共24小时。在72小时时，通过对股动脉标本进行光镜和电镜检查来评估对血液注入和治疗的反应。
光镜检查时，第1组、第2组和第3组动脉管腔的平均直径分别为514.47±15.3、317.63±12.1和503.91±9.6微米。在24小时时，第1组动脉壁的平均厚度为77.69±4.2微米。第2组的这一平均厚度增加到164.82±9.1微米。第3组经GYKI治疗后，动脉壁的平均厚度为95.37±5.3微米。在第2组大鼠中，电镜显示出各种变化，包括股动脉壁明显的管腔狭窄和壁增厚。最显著的发现是内皮的退行性变化，表现为内弹性膜呈波纹状外观。第3组大鼠的内皮略有收缩，平滑肌细胞松弛；与第2组大鼠相比，这些大鼠血管壁和内弹性膜的变化不那么明显。
本研究结果表明，GYKI 52466在大鼠模型中抑制AMPA受体并诱导股动脉壁平滑肌细胞松弛。该物质可能是治疗脑血管痉挛的一种保护和治疗剂。
